Pancreatic cancer remains one of the most lethal cancers, due to a lack of effective detection methods, invasive surgical treatments, and early spread and metastasis. Better therapeutic approaches are needed, along with improved means for detecting and staging pancreatic cancer. Prostate stem cell antigen (PSCA), originally identified as a marker in prostate cancer, is highly expressed in most pancreatic cancers including pancreatic adenocarcinoma. Antibodies recognizing PSCA are currently in a clinical evaluation for treatment of pancreatic cancer. In Phase I, humanized, affinity-matured anti-PSCA engineered antibody fragments including a minibody (80kDa single-chain Fv-CH3) and a cys-diabody (50 kDa signle-chaing Fv dimer) were generated, and show rapid tumor targeting and blood clearance, optimal for PET imaging applications. A lead anti-PSCA cys-diabody was selected for development. Phase II will include (1) Continue clinical product development of the lead anti-PSCA Cys-Diabody in microbial system and conduct testing and toxicity studies required for regulatory filing. (2) Optimize a radiolabeling strategy for PSCA cys-diabody and conduct biodistribution and imaging studies, to optimize the clinical conjugation and radiolabeling strategy for the PSCA cys-diabody.